This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The efforts of my research group focus on understanding the molecular mechanisms of lentiviral persistence and pathogenesis using human and animal virus systems, e.g. human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and equine infectious anemia virus (EIAV). A major focus of our studies of lentiviral persistence is the characterization of the evolution of viral populations during various stages of disease, the compartmentalization of viral quasispecies to different tissues during persistent infection, and the effects of viral variation on viral immunological properties. These HIV-1 evolution studies are performed in HIV-1 infected subjects that are part of the NIH-funded Multicenter AIDS Cohort Study. In parallel to these HIV-1 studies, experimental infections of monkeys with SIV or horses with EIAV are utilized to examine the nature and role of genomic and antigenic variation in viral persistence and pathogenesis.